Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab

Eline De Keyser, Celine I Busard, Sven Lanssens, Lieve Meuleman, Barbara A Hutten, Antonio Costanzo, Juul M van den Reek, Jeffrey Zweegers, Jo Lambert, Phyllis I Spuls

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BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine.

METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment.

RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164).

CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

Original languageEnglish
Pages (from-to)634-639
Number of pages6
JournalTherapeutic drug monitoring
Issue number5
Publication statusPublished - 1 Oct 2019

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